Clinical Study Of Liver Regeneration In Living Donor Liver Transplantation

Part 1 Liver regeneration in living donor liver transplantationObjective:Liver regeneration after the loss of hepatic tissue is a fundamental response to liver injury.There was only part of the liver in living donor liver transplantation.the partial-liver grafts may not be an optimal size for adult recipients. The donors donated most of the liver, so their liver volume sharp dropped. That needs liver regeneration to meet the needs. The purpose of this study was to investigate the regeneration of graft liver after living donor liver transplantation. By analysis relation of factor which may be likely to affect liver regeneration and liver regeneration, we should accumulate experience for future of living donor liver transplantation.Methods:Data of 86 consecutive LDLT cases from June,2007 to December,2008, operated and managed by the same surgical team were retrospectively analyzed. Two cases in which recipients because of early postoperative death, be ruled out, one case of liver transplant recipients after a sudden unexplained liver failure secondary cadaveric liver transplantation was performed immediately to save lives to be ruled out. Object of study include 86 donors and 83 recipients. Clinical index:1. general state of health of donors and recipients before operation; 2. check post-operation ALT/AST/TBIL of donors and recipients.The total liver volume, right lobe liver volume and left liver volume were measured by CT before surgery and two weeks after operation. We weighed the actual right liver. We would compare the volume ratio of the regenerated left lobe to the original left lobe before hepatectomy and the left lobe proportion preoperatively, and compare liver regenerating rate of donors and recipients. The donor age, sex, liver steatosis and the middle hepatic vein if were harvested as the impact of donor and recipient liver regeneration and recovery of liver function factors were analyzed. Statistical analysis was done using SPSS 17.0 data processing package, all the measurement data were analyzed for normality, normal distribution of the results to mean±standard deviation (x±s) said, compared with a single factor analysis of variance and t test, LSD pairwise comparison; skewed distribution results in the median that were analyzed by Mann-Whitney test and Kruskal-Wallis test. Correlation analysis using binary variables set from the simple Pearson correlation coefficient, P value <0.05 was considered significant difference. Results:1. The liver volume measured through CT showed positive correlation with liver weight measured intraoperatively.2. Both donors and recipients showed immediate increases in liver volume. The liver regenerated significantly faster and reached a higher peak in recipients than in donors.3. The volume ratio of the regenerated left lobe to the original left lobe before hepatectomy was inversely proportional to the left lobe proportion preoperatively. This strong but inverse correlation reflected the good regenerative ability of the remnant left lobe .The volume ratio of the regenerated transplanting lobe to the original donor's right lobe before hepatectomy was positively proportional to the ESLV of recipient preoperatively.4. According to the standards set by the preoperative assessment, donor age, sex and degree of liver steatosis after 2 weeks for donor and recipient did not affect regeneration of remnant liver volume. The postoperative residual liver regeneration rate of the MHV non-harvest group should be greater than the MHV harvest group, and for recipients of liver regeneration after transplantation were no difference. 5. Postoperative donor liver function (ALT/AST/TBIL) recovery was not affected by donor age, sex and degree of liver steatosis, and the MHV. In the current donor selection criteria the donors were safe. Recipients'liver function was affected by liver steatosis in the early postoperation, but no significant difference after two weeks. Others were not found significant differences.Conclusions:Restoration of liver volume occurred rapidly after transplantation, and regenerated more rapidly in recipients than in donors, but followed different patterns in donors and recipients. Deviation from these patterns warrants further investigation. Donors' liver volume in the MHV non-harvest group restorated more rapidly than in the MHV harvest group. There was no difference of liver regenerating rate between the recipients of the MHV harvest group and the MHV non-harvest group. Because the grafts liver in the MHV non-harvest groupⅤ,Ⅷsegment hepatic vein would be reconstructed Part 2 Algorithm of middle hepatic vein donor with a remnant liver volume rate≤35% in adult-to-adult right lobe living donor liver transplantationObjective: The treatment algorithm of donor middle hepatic vein (MHV) was focal point in living donor liver transplantation, especially for donors with a remnant liver volume of less than 35%. This study's aim was for liver regeneration and Prognosis of donors with a remnant liver volume rate less than 35%.Methods:Data of adult-to-adult right lobe LDLT cases from March,2008 operated and managed by the same surgical team according to the pre-operation MHV treatment algorithm were analyzed. We should study the donor with a remnant liver volume rate less than 35%.1,According to the liver volume measured by CT, there should be GV/R-ESLV> 40% and RLV%>30% in living donor liver transplantation.2,we should study donors with RLV%<35%: a)when GRWR>1.0%, we were prone to no MHV; b)when GRWR<1.0%, we should comprehensively considere branches of each hepatic vein and the venous flow of theⅣ,Ⅴ,Ⅷsegment, combining with donor liver steatosis, donor age, recipient age and recipient preoperative status (Meld score and Child classification) and other factors carefully to allocate middle hepatic vein.The donors of this study were failed into two groups:the MHV harvest group and the MHV non-harvest group, we should comprehensively study the branch of MHV through IQQA system, Hepatic venous ofⅣ,Ⅴ,Ⅷsegment should been assessed quantitatively through IQQA software. clinical index:1,general state of health of donors and recipients before operation; 2,check post-operation ALT/AST/TBIL of donors; 3,complication of donors in perioperation. We measured total liver volumes and lobar liver volumes of donors before operation and 2week after operation. There were 11 donors in the MHV non-harvest group, and 9 donors the MHV harvest group. Statistical analysis was done using the Statistical Package for the Social Science(SPSS) version 17.0. All the measurement data were analyzed for normality, normal distribution of the results to mean±standard deviation (x±s). The sudent's T-test was used. A p value<0.05 was considered statistically significantResults:1. There was significant difference in donor age, BMI, gender, operation time,blood loss,blood transfusion,hospital day and RLV% between the MHV harvest group and the MHV non-harvest group.2. Their liver function was recovery when they discharged from hospital; ALT of the MHV non-harvest group was higher than the MHV harvest group, The peak post-operative values of AST,T-bilirubin was no different. There was no severe surgical complication in two groups.3. Donor liver of the MHV non-harvest group regenerated faster than the MHV harvest group after 2 weeks post-operation; there was no difference at 4weeks.Conclusion: That middle hepatic vein was harvested had some influence for early postoperative donor liver function and regeneration, but does not affect the final restoration. The MHV treatment algorithm with IQQA system for donors with a remnant liver volume of less than 35% is safe to donors. Part 3 Relationship between peripheral blood-related factors and liver regeneration in living donor liver transplantationObjective:Although the ability of the liver to regenerate to a predetermined size after resection made adult-to-adult living donor liver transplantation (LDLT) possible, there is little information regarding the growth regulatory mechanism for a small-for-size liver. Detecting serum growth factors and cytokines of donors and recipients can help us better understand the in vivo regulatory mechanisms of liver regeneration after living donor liver transplantation. We investigated the postoperative changes in serum levels of growth factors (hepatocyte growth factor (HGF), epidermal growth factor (EGF), vascular epidermal growth factor (VEGF), transforming growth factor-α(TGF-α), and transforming growth factor-β1(TGF-β1)) and cytokine(Interleukin-6(IL-6) and Tumor necrosis factor-α(TNF-α)). We would compare these factors and liver regeneration.Methods:Data of 26 consecutive adult-to-adult LDLT cases from January to December, 2009, operated and managed by the same surgical team were analyzed. Donors were falled into the MHV harvest group and the MHV non-harvest group, and so recipients. Clinical index:1. general state of donors and recipients before operation; 2. Portal venous flow in the operation; 3. post-operation ALT/AST/TBIL of donors and recipients. We would measured HGF,EGF,VEGF,TGF-α,TGF-β,IL-6 and TNF-αin peripheral blood in donors and recipients before and 1,3,7,14 day after operation through ELISA. We measured liver volumes before operation and 2 week after operation. The different levels of these factors were compared according to each group at different time points. There was comparison of two intraoperative portal vein blood flow of two recipients groups. The rates of liver regeneration were compared for donors and recipients in two weeks after surgery. Statistical analysis was done using SPSS 17.0 data processing package, all the measurement data were analyzed for normality, normal distribution of the results to mean±standard deviation (x±s) said, compared with a single factor analysis of variance and t test, LSD pairwise comparison; skewed distribution results in the median that were analyzed by Mann-Whitney test. Correlation analysis using binary variables set from the simple Pearson correlation coefficient, P value <0.05 was considered significant difference. Results1,Hyperplasia after liver volume was significantly higher for recipients than donors, for donors of the MHV non-harvest group than the MHV harvest group, no difference between the two groups of recipients. The intraoperative portal venous flow rate correlated significantly with regeneration of the partial-liver allograft of recipients in LDLT at 2 weeks.2,Intraoperative portal vein blood flow had a positive correlation with liver regeneration of recipients in two weeks after transplantation.3,The epithelial growth factor (EGF), vascular epithelial growth factor (VEGF), interleukin -6 (IL-6) and tumor necrosis factor-a (TNF-a) in peripheral blood of donor and recipient were found no significant difference in every time point before and after operation.4,The hepatocyte growth factor (HGF) in peripheral blood of donors and recipients increased to a maximum at first day after operation, and then decreased slowly. HGF in peripheral blood of donors decreased to preoperative levels at 1 week after operation. The HGF levels in the MHV non-harvest group were significantly higher than the MHV harvest group on first and third day after surgery; The HGF level of ricipients in vivo has been higher than the donorThe transforming growth factor-a (TGF-a) in peripheral blood donors and recipients increased to the maximum in the first postoperative day, then gradually decreased by day 14 after surgery to normal. There was no significant difference between the two groups donors, but for the recipients and donors in the first and third postoperative day, the difference was statistically significant.The transforming growth factor-β1 (TGF-β1) in donor and recipient peripheral blood in the first postoperative day was significantly higher than before surgery, but reached the peak in the third postoperative day and then decreased. The TGF-β1 levels in the MHV non-harvest group were significantly higher than the MHV harvest group on 7th and 14th day after surgery; The TGF-β1 level of ricipients in vivo has been higher than the donor on 1st, 3rd and 7th day after surgeryConclusion: The intraoperative portal venous flow rate correlated significantly with regeneration of the partial-liver allograft of recipients in LDLT at 2 weeks. Significantly increased HGF and TGF-β1 serum levels after living donor liver transplantation demonstrate its crucial role among the other investigated growth factors in regeneration of the remnant liver tissue during the early period after the operation, but TGF-a's role needs further study. This study shows that the part liver would show the rapid proliferation immediately after surgery in living donor liver transplantation that was regulated by HGF and TGF-β1. The elevated levels of HGF accelerated liver regeneration after living donor liver transplantation, with the attendant increased TGF-β1 to control the size of the liver. TGF-β1 played an important role on the control part of the liver back to the standard liver volume. According to these two factors in donors and patients we supposed supposed that a growth regulatory mechanism of small-for- size liver graft in LDLT between donors and recipients was same.